Coop's Corner #4: Alpha-2 Antagonism? Yes Please.

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    Post Coop's Corner #4: Alpha-2 Antagonism? Yes Please.


    As many of you may already know, alpha-2-antagonists are simply compounds that antagonize the alpha-2-adrenoreceptor. The most popular ones are yohimbine, rauwolscine, and a variety of yohimbe alkaloids.

    These 3 categories of alpha-2-antagonist each possess a unique goal-specific attribute, but before we delve into specifics, let's look at how effective these compounds are for fat loss.

    The relevant research on this topic shows that yohimbine is extremely effective for fat loss.

    Yohimbine: the effects on body compos... [Res Sports Med. 2006 Oct-Dec] - PubMed - NCBI

    The researchers didn't just use anyone. They used lean athletes. How lean? Both groups started at roughly 9% bodyfat. To put that in perspective:



    So these guys are shredded. And they're active, so they probably have a good deal of LBM. After 21 days of yohimbine supplementation, placebo remained unchanged but the yohimbine group lost about 2% bodyfat, taking them all the way to 7% BF. No significant changes in muscle mass or performance were noted.

    So:

    3 weeks of Yohimbine supplementation caused a 2% reduction in bodyfat from an already shredded baseline of 9% BF, all the while preserving muscle mass and strength/endurance.


    To put this in perspective, again refer to the bodyfat chart. These athletes went from the far right image to the middle image in 3 weeks, without major changes to diet or exercise regimens. That's extremely impressive.



    So which form of yohimbine is best? That'll depend on your goals.

    Yohimbine possess extreme affinity for the alpha-2-adrenoreceptor, but due to receptor homology with various 5-HT receptors, yohimbine HCl is highly anxiogenic and is clinically used to model panic disorder. The effective dose is 0.2mg/kg in isolation. If you combine any of these alpha 2 antagonists with caffeine or beta-agonists (aka synergists), the necessary dose decreases quite a bit.

    Rauwolscine lacks significant activity at the 5HT receptors, but it has its own issues. It's less potent than yohimbine, requiring a markedly higher dose to elicit the same effects. Furthermore, it's partially adrenolytic, as it is less selective than yohimbine on the adrenergic system, partially antagonizing alpha-1- adrenoreceptors.

    And then we have the various yohimbe alkaloids like 11-OH yohimbine, that are alpha-2-antagonists (not to be confused with a broad-spectrum extract of alkaloids). These compounds act similarly to yohimbine for fat loss but seem to promote a feel-good energy as well. They also have significantly longer half-lives than either yohimbine or rauwolscine, making them a great choice earlier in the day.

    So which one works best? It's goal-specific. The most effective for fat loss will be yohimbine or yohimbe alkaloids. The most effective for someone prone to anxiety will be rauwolscine or yohimbe alkaloids (if you have anxiety disorder, you should not be using any of these).

    What works best with alpha-2-antagonists? Well here's a brief physiology lesson. The alpha-2 receptor is an autoreceptor, meaning it is located NOT on the postsynaptic neuron chiefly, but on the pre-synaptic neuron. It acts to PREVENT further release of fat burning catecholamines: this is why we want to antagonize (inhibit) it. It's thought that stubborn fat is particularly rich in these alpha-2-receptors, hence why fat loss is always inhibited in these regions. For those seeking to lose stubborn fat, alpha-2-antagonists are a great option.

    Alpha-2 antagonists synergize with anything that potentiates catecholamine release. This means caffeine, exercise, forskolin, and beta-agonists all work exceptionally well with alpha-2 antagonists. Furthermore, because alpha-2 antagonism can increase insulin release, these compounds are best taken fasted. A fasted state promotes the counter-regulatory cascade anyway (increased NE/E), so it's the perfect time to dose these, along with preworkout dosing.




    So, in summary:

    1. Yohimbine or Yohimbe alkaloids are the preferred choice for fat loss; rauwolscine or yohimbe alkaloids may be preferred if one is prone to anxiety.
    2. The recommended dose for yohimbine is 0.2mg/kg BW in isolation. If you take it with synergists, the dose needed is less. Rauwolscine needs a higher dose.
    3. These compounds have been found to be extremely effective for fat loss, even if you're already very lean and borderline-contest ready. There is also a considerable body of data showing they help with erections. If there's one supplement to consume orally for stubborn fat loss, it's an alpha 2 antagonist.
    4. These compounds synergize with caffeine, exercise, forskolin, or beta-agonists. They should be dosed in a fasted state or prior to exercise for maximum results.
    5. Recommended products:

    a. PES Alphamine
    B. iForce Dexaprine XR
    c. ECY (use extreme caution)
    d. PES Alpha-T2
    e. OxyElite Pro with Purple Top
    f. PES Enhanced
    g. Muscletech Hydroxystim
    h. Athletix Acute FX

    *Yohimbine should be avoided in concert with Tyrosine or in those diagnosed with anxiety disorder.
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    This is awesome info
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    Coop these are awesome.
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    Very informative post, thanks Coop! I can attest to the significant fat loss effects that alpha-2-antagonists have in already lean individuals. Im fairly lean right now myself and at 2 weeks in with alphamine I continue to get leaner
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    Hey Coop,

    Are there any other alpha-2 antagonists besides rauwolscine or yohimbe? I can't tolerate either. 1/2 a scoop of PES Enhanced makes my stomach upset and gives me the shakes.
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    Thanks everyone.

    Quote Originally Posted by Patuba View Post
    Hey Coop,

    Are there any other alpha-2 antagonists besides rauwolscine or yohimbe? I can't tolerate either. 1/2 a scoop of PES Enhanced makes my stomach upset and gives me the shakes.
    Unfortunately, some users will experience these effects from alpha-2 antagonists due to excessive adrenergic stimulation. It won't matter which alpha-2 antagonist you use, the story will be the same. Your only real hope is the tolerance that develops with continued use. There's evidence that the adrenergic effects diminish with time while lipolysis actually stays constant
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    Thanks for the info. I can tolerate ephedrine fine, just not alpha 2 antagonists. I might attempt to slowly build a tolerance.
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    Quote Originally Posted by mr.cooper69 View Post
    Thanks everyone.



    Unfortunately, some users will experience these effects from alpha-2 antagonists due to excessive adrenergic stimulation. It won't matter which alpha-2 antagonist you use, the story will be the same. Your only real hope is the tolerance that develops with continued use. There's evidence that the adrenergic effects diminish with time while lipolysis actually stays constant
    Bingo. I highly recommend people using yohimbine for the first time to start low, and assess tolerance before just going by the recommended dosage of 0.2mg/kg.
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    My body response very well to yohimbe.
    Rawsc on the other hand, can't take the stuff. Leaves me with terrible heartburn and upset stomach for hours.
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    Any thoughts on intramuscular injections of Yohimbine for greater results?
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    Quote Originally Posted by Daycrawler View Post
    Any thoughts on intramuscular injections of Yohimbine for greater results?
    I think it would be beyond stupid
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    Nice write up coop. As always, great info
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    Quote Originally Posted by mr.cooper69 View Post

    I think it would be beyond stupid
    How about the transdermal approach vs oral? As effective, more effective or less...?
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    Quote Originally Posted by schizm View Post

    How about the transdermal approach vs oral? As effective, more effective or less...?
    Of course. Its what's in eviscerate topical by evomuse along with much more
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    Quote Originally Posted by nattydisaster View Post
    I want to be like cooper when I grow up
    Me too.

    Loving these threads. This one was very well done and super easy to understand.
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    Quote Originally Posted by JD261985 View Post

    Of course. Its what's in eviscerate topical by evomuse along with much more
    Lol, yes I'm aware and really like evis/smolder, they are effective, but that doesn't mean they are as effective or better than oral yohimbine...
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    Quote Originally Posted by mr.cooper69 View Post
    Thanks everyone.



    Unfortunately, some users will experience these effects from alpha-2 antagonists due to excessive adrenergic stimulation. It won't matter which alpha-2 antagonist you use, the story will be the same. Your only real hope is the tolerance that develops with continued use. There's evidence that the adrenergic effects diminish with time while lipolysis actually stays constant
    Intrigued...
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    Hey Coop - great write up...Spot on and understandable!

    It was asked above...but are there other alpha-2 antagonists beyond yohimbine and related moieties that could do the same trick (even if perhaps slightly less efficaciously). Yohimbine is banned in Canada and most international countries...
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    Quote Originally Posted by Daycrawler View Post
    Any thoughts on intramuscular injections of Yohimbine for greater results?
    duchaine used to experiment with injecting yohimbine directly sub Q into stubborn fat pockets on women. as I recall he felt while it worked the process included several very small injections thus making the process quite tedious and a little painfull for the women.
    @ coop : what about a TD?
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    Quote Originally Posted by braco1 View Post
    Hey Coop - great write up...Spot on and understandable!

    It was asked above...but are there other alpha-2 antagonists beyond yohimbine and related moieties that could do the same trick (even if perhaps slightly less efficaciously). Yohimbine is banned in Canada and most international countries...
    Higenamine would be one albeit less potent when compared to yohimbine. The short half life and bioavailability are concerns however, Coop may know of more.
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    Quote Originally Posted by xR1pp3Rx View Post
    duchaine used to experiment with injecting yohimbine directly sub Q into stubborn fat pockets on women. as I recall he felt while it worked the process included several very small injections thus making the process quite tedious and a little painfull for the women.
    @ coop : what about a TD?
    SubQ or TD may be effective. Intramuscular, conversely, would be a death sentence
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    Quote Originally Posted by xhrr View Post
    Higenamine would be one albeit less potent when compared to yohimbine. The short half life and bioavailability are concerns however, Coop may know of more.
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    Quote Originally Posted by mr.cooper69 View Post
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    Quote Originally Posted by mr.cooper69 View Post
    A
    *Yohimbine should be avoided in concert with Tyrosine or in those diagnosed with anxiety disorder.
    This is good to know, just realized I have been mixing two different products, one with yohimbine, the other with Tyrosine. I have been researching why it is bad to mix these but have had no luck. Can you maybe give me some more detailed info, Coop? Any other supplements I should be careful mixing with yohimbine?!
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    Quote Originally Posted by mr.cooper69 View Post

    3 weeks of Yohimbine supplementation caused a 2% reduction in bodyfat from an already shredded baseline of 9% BF, all the while preserving muscle mass and strength/endurance.

    To put this in perspective, again refer to the bodyfat chart. These athletes went from the far right image to the middle image in 3 weeks, without major changes to diet or exercise regimens. That's extremely impressive
    .

    So just to clarify if I kept me diet and training the same and added this into my supplementation I would drop body fat and maintain LBM and strength? Don't mean to sound like a smart ass if that's how it comes off :/
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    Quote Originally Posted by SoupNaziNazi View Post

    So just to clarify if I kept me diet and training the same and added this into my supplementation I would drop body fat and maintain LBM and strength? Don't mean to sound like a smart ass if that's how it comes off :/
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    Quote Originally Posted by SoupNaziNazi View Post
    So just to clarify if I kept me diet and training the same and added this into my supplementation I would drop body fat and maintain LBM and strength? Don't mean to sound like a smart ass if that's how it comes off :/
    Consider footballers (soccer players) especially at the professional level do a large volume of running for endurance throughout their preparation. Thus it is not wise to expect a 2% BF drop in 3 weeks for the average lifter.

    Also I assume A2 antagonism is best used pre cardio, how effective will it be if taken in a sedentary state..?
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    Quote Originally Posted by Philosophy View Post

    Also I assume A2 antagonism is best used pre cardio, how effective will it be if taken in a sedentary state..?
    He wasn't saying he was sedentary necessarily, just that he wouldn't make any changes to his current training routine.
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    Quote Originally Posted by Jon_b View Post

    He wasn't saying he was sedentary necessarily, just that he wouldn't make any changes to his current training routine.
    I never directed the sedentary idea towards him, rather was asking if anyone knows how less effective it is in such a state.

    As for him, I told him to be wary that footballers run considerable distances regularly.
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    Quote Originally Posted by SoupNaziNazi View Post
    So just to clarify if I kept me diet and training the same and added this into my supplementation I would drop body fat and maintain LBM and strength? Don't mean to sound like a smart ass if that's how it comes off :/
    Yes, that's what placebo control is for. All factors were controlled for
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    Awesome write up man.
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    Quote Originally Posted by lpfleiderer View Post
    This is good to know, just realized I have been mixing two different products, one with yohimbine, the other with Tyrosine. I have been researching why it is bad to mix these but have had no luck. Can you maybe give me some more detailed info, Coop? Any other supplements I should be careful mixing with yohimbine?!
    The issue is that yohimbine increases the production of catecholamines and also blocks subsequent catecholamine metabolism. In principle, you should also avoid supplements or foods that contain high amounts of phenylalanine.
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    Quote Originally Posted by Synapsin View Post
    The issue is that yohimbine increases the production of catecholamines and also blocks subsequent catecholamine metabolism. In principle, you should also avoid supplements or foods that contain high amounts of phenylalanine.
    To piggyback: http://forum.bodybuilding.com/showth...2083131&page=1

    The FDA issued warning letters about the combination. Sorry mods for the other forum link, but this thread was actually informative
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    Coop, the series of threads you have been writing up have been great. I appreciate the time you put into these.
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    Hate the dosing protocol of Y, or I would use it more often :/
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    Quote Originally Posted by mr.cooper69 View Post
    To piggyback: http://forum.bodybuilding.com/showth...2083131&page=1

    The FDA issued warning letters about the combination. Sorry mods for the other forum link, but this thread was actually informative
    There was a particular energy drink sold in gas stations everywhere that had yohimbine and tyramine combined that had a lot of side effects and led to the initial trouble behind the combos.

    The street term for this effect is called "cheesing". No...not the same cheesing from South Park

    It received the name because cheese is high in tyramine. So if you are getting bad reactions to yohimbine/alpha-2 antagonists and there is a lot of cheese in your diet that day, you may have found your problem.

    http://en.wikipedia.org/wiki/Tyramin...d_pharmacology
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    I recently tried a few fat burners from various companies, including Alphamine. All had some kind of yohimbine or rauwolscine in them. I got headaches from all of them, and generally felt awful while they were in my system. My heart rate didn't go way up or anything, but it made me *feel* hypertensive. The only one that didn't make me feel like that was Red Acid Reborn, but it still gave me enough of a headache that I wouldn't want to deal with the effects daily, or hit the gym while I was taking it.

    I know that caffeine isn't the problem because I drink a good amount of coffee daily, and I can take (yohimbine-free) PWOs without any issue. Is this a normal response to the dosages of yohimbine common in these kinds of products?

    Oh, and kudos to you guys and other companies willing to send out samples of these kinds of products so we can figure out if they work for our bodies before we buy them. I know now that I won't be buying any Alphamine in the future (unless the UK version starts selling for the same price as the US version on NP), but I did get three bottles of Forskolin 95 in the mail yesterday. ;-)
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    Killer information, Coop.
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